Open AccessFully human antibody exhibits pan‐human leukocyte antigen‐DR recognition and high in vitro/vivo efficacy against human leukocyte antigen‐DR‐positive lymphomas
Author(s) -
Tawara Tomonori,
Hasegawa Kazumasa,
Sugiura Yusuke,
Tahara Tomoyuki,
Ishida Isao,
Kataoka Shiro
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00469.x
Subject(s) - epitope , human leukocyte antigen , antibody , biology , antigen , monoclonal antibody , immunology , lymphoma , cytotoxicity , allele , microbiology and biotechnology , in vitro , virology , gene , genetics
HD8, a fully human monoclonal antibody specific for human leukocyte antigen‐DR (HLA‐DR), was generated by using the transchromosome mouse that bears the human immunoglobulin genes. HD8 could bind to all 13 tested HLA‐DR‐positive cell lines and 35 B‐cells from healthy donors. Epitope mapping revealed that while the antibody recognizes the most polymorphic region of the HLA‐DRB chain, its critical epitope residues are conserved in the major alleles. Indeed, HD8 could recognize 99.2% of HLA‐DRB alleles. Since its essential epitope residues are also largely conserved in HLA‐DP and HLA‐DQ, HD8 could recognize 100% and 66% of the HLA‐DP and HLA‐DQ alleles tested, respectively. HD8 exerted strong antibody‐dependent cellular cytotoxicity and complement‐dependent cytotoxicity in vitro , and significantly extended the life span of immunocompromised mice inoculated with non‐Hodgkin lymphoma cell lines. The HD8 antibody may be highly useful in HLA‐DR‐targeted immunotherapy as it is likely to evoke similarly strong responses in individuals carrying different HLA‐DR alleles. ( Cancer Sci 2007; 98: 921–928)